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Ruifang Sui, Xuan Zou, Zhongqi Ge, Hui Li, Mingchu Xu, Rui Chen, Fangtian Dong; Phenotypic Variability in RDH12 Retinopathy. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3138.
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© 2017 Association for Research in Vision and Ophthalmology.
To investigate phenotypic variability and to report genetic defects in a cohort of Chinese patients with mutations in RDH12 gene.
26 patients from 22 unrelated families with bi-allelic pathogenic RDH12 mutations were studied. Detailed ophthalmologic examination, fundus photography, spectral domain optical coherence tomography (SD-OCT), and electroretinogram were performed. Systematic next-generation sequencing (NGS) data analysis, Sanger sequencing validation, and segregation analysis were utilized to identify the pathogenic RDH12 mutations.
21 different mutations in RDH12 were detected in 22 families in the study, with 5 (23.8%) of these changes being novel. Among the patients, 13 probands were diagnosed as early-onset severe retinal dystrophy (EOSRD), 4 probands as Leber congenital amaurosis (LCA), and 4 probands as autosomal recessive retinitis pigmentosa (ARRP). Interestingly, we identified 1 proband as cone rod dystrophy (CRD). Characteristic RDH12 retina phenotype includes: type 1, the petal-like macular coloboma with surrounding pigment changes; type 2, wide-spread pigment changes, RPE atrophy and “gold foil refection” maculopathy; type 3, heavy and confluent pigment proliferation involving the macular region. type 4, posterior pole atrophy with relatively normal peripheral retina. OCT showed macular depression and chorioretinal atrophy without normal lamination structure. One patient has numerous whitish-yellow subretinal spots scattered at the mid-periphery and para-fovea. Pre-retinal hemorrhage was observed in one patient. ERG recording- ranges from non-recordable in LCA to mildly declined in ARRP, and one CRD patient revealed substantially diminished cone response with relatively preserved rod response. Mutation p.V146D is the most frequent variant, which accounts for 20.5% of the patients. 75% ARRP patients carry missense or non-frameshift changes in both alleles, while at least one loss of function allele was present in near 50% of early onset retinal dystrophy cases.
Variable but characteristic phenotypes were observed in RDH12 retinopathy. RDH12 mutation is the common cause of early onset retinal dystrophy. Loss of function allele is more frequent in EOSRD and LCA than that in ARRP and CRD cases. To the best of our knowledge, this is the first report of RDH12 associated cone-rod dystrophy.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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